Anti-tumour activity of CS-7017, a selective peroxisome proliferator-activated receptor gamma agonist of thiazolidinedione class, in human tumour xenografts and a syngeneic tumour implant model

Abstract

The anti-tumour activity of the novel thiazolidinedione class peroxisome proliferator-activated receptor gamma (PPARγ) agonist CS-7017 was investigated. CS-7017 activated PPARγ-mediated luciferase expression with an EC50 of 0.20nM. In addition, CS-7017 was shown to be highly selective for PPARγ amongst other PPAR subfamilies. CS-7017 inhibited the proliferation of the human anaplastic thyroid tumour cell line DRO and the pancreatic tumour cell line AsPC-1 in vitro at concentrations as low as 10nM. In xenograft studies, CS-7017 inhibited the growth of the human colorectal tumour cell line HT-29 in nude mice as well as DRO in nude rats in a dose-dependent manner. At the same dose, an increase in the levels of adiponectin, a surrogate marker for PPARγ activation, was also observed. CS-7017 prolonged the survival of mice inoculated with murine colorectal tumour Colon 38 with marginal tumour growth inhibition. These preclinical results support the potential utility of CS-7017 in a clinical setting.